New host DNA specificity systems Pae 610 and Pae 603

Institute of Biochemistry of Plants, Academy of Sciences of the Georgian SSR, Tbilisi. Institute of Biological and Medical Chemistry, Academy of Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR S. S. Debov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 7, pp. 91–94, July, 1991.     

Specific Buffers Affect the Stability of a Charged Cyclodextrin Complex Via Competitive Binding and Ionic Strength

The effect of 11 buffers as well as the effect of ionic strength were investigated on the binding between the bile salt taurochenodeoxycholate and the ionic sulfobutylether-β-cyclodextrin. The investigations showed that both ionic strength and competitive binding affected the stability constant. The stability constant for the sulfobutylether-β-cyclodextrin complex increased from 34,400 M^?1 to 114,000 M^?1 as the ionic strength of the solution increased to 0.15 M. Keeping the ionic strength constant, the stability constant for the complex depended on the buffer in the solution, with citric and succinic acid reducing the stability constant. The reduction in the stability constant by buffers was related to a competitive mechanism. The results showed that, when accounting for the variation in ionic strength between the buffers, three groupings of buffers existed. All carboxylic acid buffers decreased the stability constant of the sulfobutylether-β-cyclodextrin complex, relative to the effect observed by altering the ionic strength, whereas the other buffers only affected the stability constant in terms of the changes in ionic strength. Both buffer species and ionic strength impacted the stability of ionic cyclodextrin complexes, hence, it is important to be aware of these effects when working with, comparing and reporting stability constants.     

Solubility of hydroxyapatite by solid titration at pH 3-4

OBJECTIVES: The solubility isotherm (S) of hydroxyapatite (HAp) is of fundamental importance to saliva chemistry, dental caries and related contexts. It has previously been shown that the locus of the S[HAp] is substantially lower than is commonly reported, and of different slope, probably due to HAps incongruent dissolution. The aim of the present study was to determine the S[HAp] over a wider pH range and to identify the precipitate formed at equilibrium in HAp solid titration. METHODS: The solid titration technique of Leung and Darvell (Leung VW-H, Darvell BW. Calcium-phosphate system in saliva-like media. J Chem Soc Faraday Trans 1991;87(11):1759-64.) was used to investigate the solubility behaviour of HAp at 37.0+/-0.1 degrees C in 100 mM aqueous KCl. The pH range studied overlapped that of earlier work from pH 3.6 to 5.2, for a reproducibility check and validation, and extended to pH approximately 2.9. XRD and EDX were used to identify the precipitates. SEM and TEM were used to observe the morphology. RESULTS: The previous S[HAp] reported by Chen et al. (Chen Z-F, Darvell BW, Leung VW-H. Hydroxyapatite solubility in simple inorganic solutions. Arch Oral Biol 2004;49(5):359-67.) was reconfirmed. An abrupt change of slope of S[HAp] was detected at pH approximately 3.9. No other phase than HAp was found at pH 3.2, 3.6 and 4.1. In particular, brushite (dicalcium phosphate dihydrate) was not detected, even below pH 3.9, where instead calcium-deficient HAp was formed. CONCLUSION: The solid titration method was reconfirmed as reproducible and to yield HAp from pH 2.9 to 5.2. The expected brushite did not appear, but rather a stable calcium-deficient HAp was consistently formed. The chemistry of calcium phosphates needs to be reevaluated.     

Acid-base and lipophilic properties of peptide nucleic acid derivatives

The first combined experimental and theoretical study on the ionization and lipophilic properties of peptide nucleic acid (PNA) derivatives, including eleven PNA monomers and two PNA decamers, is described. The acidity constants (pK_a) of individual acidic and basic centers of PNA monomers were measured by automated potentiometric pH titrations in water/methanol solution, and these values were found to be in agreement with those obtained by MoKa software. These results indicate that single nucleobases do not change their pK_a values when included in PNA monomers and oligomers. In addition, immobilized artificial membrane chromatography was employed to evaluate the lipophilic properties of PNA monomers and oligomers, which showed the PNA derivatives had poor affinity towards membrane phospholipids, and confirmed their scarce cell penetrating ability. Overall, our study not only is of potential relevance to evaluate the pharmacokinetic properties of PNA, but also constitutes a reliable basis to properly modify PNA to obtain mimics with enhanced cell penetration properties.     

Potentiometric Titration of 2-Thiouracils

A new method is presented for the determination of 100–500 μmol of 6-methyl-2-thiouracil and 6-benzyl-2-thiouracil which utilises their reaction with iodine in an alkaline medium with potentiometric end-point detection. Elaborated methods were applied to the determination of 2-thiouracils in drugs.     

半夏及不同炮制品中总游离有机酸含量比较

目的建立半夏及其不同炮制品中总游离有机酸的含量测定方法,比较半夏及其炮制品中总游离有机酸的含量。方法采用电位返滴定法,以琥珀酸为对照品,测定生品及炮制品中总游离有机酸的含量。结果分别测定了3批生品及清半夏、姜半夏中游离有机酸含量,姜半夏和清半夏中游离有机酸含量相对于生品有不同程度的提高。加样回收率为95．20％,RSD=1．81％。结论本法简便、准确、可靠,可作为半夏及其炮制品清半夏和姜半夏中游离有机酸测定方法。     

Solubility of TTCP and β-TCP by solid titration

Objective

Using solid titration with hydroxyapatite (HAp) and octacalcium phosphate, HAp has been found to be more stable than dicalcium phosphate dihydrate (DCPD) even at lower pH, inconsistent with the widely reported view that DCPD is less soluble than other calcium phosphates below pH 4.2. A check of the behaviour of other calcium phosphates (TTCP; Ca/P: 2.00 and β-TCP; Ca/P: 1.33) is necessary.

Methods

Solid titration was used to determine the effective solubility of TTCP and β-TCP in 100 mM KCl solution at 37.0 ± 0.1 °C for pH ∼2.9-9.2 and ∼3-7.4 respectively. The constitution of the precipitate was determined by XRD, particle morphology was observed by SEM and TEM, and the precipitate Ca/P ratio was calculated by EDX.

Results

The only identified solid phase at equilibrium was HAp at both pH 3.60 and 4.50; no residual titrant or other phases were detected. A marked change of slope in the curve occurred at pH ∼3.9 for TTCP.

Conclusion

HAp was verified to be more stable than other calcium phosphates, especially at lower pH. That DCPD is more stable below pH 4.2 is contradicted.     

Using drug-excipient interactions for siRNA delivery

SiRNA is the trigger of RNA interference, a mechanism discovered in the late 1990s. To release the therapeutic potential of this versatile but large and fragile molecule, excipients are used which either interact by electrostatic interaction, passively encapsulate siRNA or are covalently attached to enable specific and safe delivery of the drug substance. Controlling the delicate balance between protective complexation and release of siRNA at the right point and time is done by understanding excipients-siRNA interactions. These can be lipids, polymers such as PEI, PLGA, Chitosans, Cyclodextrins, as well as aptamers and peptides. This review describes the mechanisms of interaction of the most commonly used siRNA delivery vehicles, and looks at the results of their clinical and preclinical studies.     

Evaluation of the physicochemical equivalence of three brands of commercially available quinine sulphate tablets from South Western part of Nigeria

Background

The relatively little resistance to quinine globally has led to an increase in its use in P. falciparum malaria especially in multi-drug resistant strains.

Objective

To evaluate the physicochemical and equivalency of three brands of quinine sulphate tablets available in South Western region of Nigeria.

Methods

The pharmaceutical and chemical equivalence of three brands of quinine sulphate tablets were assessed through the evaluation of some biopharmaceutical parameters and active drug content.

Results

All the brands complied with the official specification for uniformity of weight. Two of the brands (A & B) gave similar crushing strengths while the third brand (C) gave a much lower value. Similarly all the brands complied with the official specification of disintegration test but the obtained values were statistically different (p<0.05). The T₇₀ obtained from the dissolution rate profile was less than 45 minutes for the three brands, although A and B were not statistically different but C was statistically from A and B. The quinine content of brands B and C are within the official specification however brand A with percentage content of 110±1.3%w/w, is above the specification while it is statistically different from the other brands.

Conclusion

Brands B and C could be regarded as chemical equivalent, but they are not biopharmaceutical equivalents, on the other hand, brands A and B may be regarded as biopharmaceutical equivalents but not chemical equivalent.